In vivo and in vitro diclofenac sodium evaluation after rectal application of soft gelatine capsules enabling application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) for controlled release.
OBJECTIVE
Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release from these systems after rectal application.


METHODS
In vitro drug release was determined in a self-constructed dissolution apparatus to simulate rectal application. For in vivo bioavailability studies rabbits were used as animal models. In vitro release and in vivo bioavailability of the capsules was compared to Voltaren suppositories.


RESULTS
The release profiles of the in vitro experiments show zero-order kinetics. The in vivo bioavailability studies show bioequivalence in terms of AUC for both formulations (capsules and Voltaren suppositories). The mean residence time (parameter of sustained release) of the capsules is three time longer in comparison to Voltaren suppositories.


CONCLUSIONS
Rectal administration of capsules provides an appropriate route for controlled release via AIT-SSLC which could be clearly verified in rabbits.
Schneeweis
A
A
Institut für Pharmazeutische Technologie, Braunschweig.
Müller-Goymann
C C
CC
D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001682:Biological Availability; D002214:Capsules; D003460:Crystallization; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D066298:In Vitro Techniques; D011817:Rabbits; D013488:Suppositories
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D013488:Suppositories; D004008:Diclofenac